How the genetic blueprints for limbs came from fish

Jan 21, 2014

This shows the expression of fish Hox genes in a mouse embryo. Credit: Denis Duboule, UNIGE

A study led by Denis Duboule shows that limbs emerged during evolution by modernisation of a preexisting DNA structure.

Our first four-legged land ancestor came out of the sea some 350 million years ago. Watching a lungfish, our closest living fish relative, crawl on its four pointed fins gives us an idea of what the first evolutionary steps on land probably looked like. However, the transitional path between fin structural elements in fish and limbs in tetrapods remains elusive.

Both fish and land animals possess clusters of Hoxa and Hoxd genes, which are necessary for both fin and limb formation during embryonic development. Denis Duboule's team, at the University of Geneva and the EPFL, Switzerland, compared the structure and behavior of these gene clusters in embryos from mice and zebrafish. The researchers discovered similar 3-dimensional DNA organization of the fish and mouse clusters, which indicates that the main genetic mechanism used to pattern tetrapod limbs was already present in fish. However, when inserted into transgenic mouse embryos, the fish Hox genes were only active in the mouse arm but not in the digits, showing that the fish DNA lacks essential genetic elements for digit formation. The study, publishing January 21, in the open access journal PLOS Biology, concludes that, although the digital part of the limbs appear first in land animals, this happened by elaborating on an ancestral, pre-existing DNA infrastructure in fish.

Duboule's team had recently shown that, during mammalian development, Hoxd genes depend on a 'bimodal' 3-dimensional DNA structure to direct the development of the characteristic subdivision of the limbs into 'arm' and 'hand', a division which is absent from fish fins.

"To determine where the genetics behind this subdivision into 'hand' and 'arm' came from during evolution, we decided to closely compare the genetic processes at work in both fin and limb development", says Joost Woltering, post-doc at the Department of Genetics and Evolution of the Science Faculty of the UNIGE and lead author of this study. Surprisingly, the researchers found a similar bimodal 3-dimensional chromatin architecture in the Hoxd gene region in zebrafish embryos. These findings indicate that the regulatory mechanism used to pattern tetrapod limbs probably predates the divergence between fish and tetrapods. "In fact this finding was a great surprise as we expected that this 'bimodal' DNA conformation was exactly what would make all the difference in the genetics for making limbs or making fins" adds Joost Woltering.

Does this imply that digits are homologous to distal fin structures in fish? To answer this question, the geneticists inserted into mice embryos the genomic regions that regulate Hox gene expression in fish fins. "As another surprise, regulatory regions from fish triggered Hox gene expression predominantly in the arm and not in the digits. Altogether, this suggest that our digits evolved during the fin to limb transition by modernization of an already existing regulatory mechanism", explains Denis Duboule.

The researchers conclude that, although fish possess the Hox regulatory toolkit to produce digits, this potential is not utilized as it is in tetrapods. Therefore, they propose that fin radials, the bony elements of fins, are not homologous to tetrapod digits, although they rely in part on a shared regulatory strategy.

New lines of investigation are to find out exactly what has changed in the DNA elements of fish versus tetrapods. "By now we know a lot of genetic switches from the mouse that drive Hox expression in the digits. It is key to find out exactly how these processes work nowadays to understand what made digits appear and favor the colonization of the terrestrial environment." concludes Duboule.

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@matt_roadhouse and verkleWHY come to a science site to deny science? especially if you have no ability to refute it? no links, valid science, no proof! You are what? Creationist?religious?Religion has no place in sciencenow... if you want to do some basic research and learn SOMETHING

Funny you keep mentioning religion when not one comment anywhere here quotes any dogma of any sort

Fossils would show an immense amount of transitional creatures instead of a very small set of bees/oysters/birds. The biggest counter argument in this is .... its too slow to show full transitions. Issue is, bodies don't just work for hundreds of generations on non-working organs/limbs etc. Everything in our body has a purpose, and these purposes are linked through thousands of networks via proteins, gene management systems, hormones etc.

We have fossil records with eons between them that show identical species with zero variation. That isn't proof though ? A few 'odd' imprints are. Keep believing the antiquated records from 1800s I guess.

assuming 100% of all living creatures that died were fossilizedwhich we know did not happen

its too slow to show full transitions

"Paleontology, evolutionary developmental biology, comparative genomics, and molecular biology contribute many advances relating to the patterns and processes that can be classified as macroevolution" [sic]

That entire article describes how every single sub-theory within macro doesn't work.

The only thing it does is try and say is micro+macro are the same, and differentiating between is solely a ploy by ID theorists.

The recent study of Genetic Entropy and the degradation of 'higher form' genomes shows that life is even susceptible to the 2nd Law of Thermodynamics

Every study done on fruit flies have been fruitless ;) Thousands of generations, even tinkering and doing our own 'natural selection' and still nothing beneficial. Certainly not moving into another higher species.

Mutations only work if within sperm/ovum since that is what passes chromosomes to make the core DNA which every host cell will carry. Even if you mutated an entire organ via insertion of circular DNA, that would not be passed via heredity. (gene therapy)

But these theories are not just about Biology, they reach into the Cosmos. Everything is set in a perfect way of mathematics and beauty, form and function.

I honestly find it crazy to say every single facet of the cosmos and life is purely random.

ID:

Amino acid molecules that form proteins, and nucleotide molecules that form DNA and RNA resist combining at any temperature. To combine, they need the help of mechanisms in a living cell or a biochemist in an organic chemistry laboratory.

DNA is made of only right-handed versions of nucleotides, while proteins are made of only left-handed versions of amino acids. Yet any random chemical reaction that produced nucleotides or amino acids would make an equal mix of left and right-handed versions of each. Even if the thousands of nucleotides needed to form a DNA molecule, or the hundreds of amino acids needed to form a protein molecule were able to combine from the mix, they would be a jumble of L+R

I am agnostic, so no religion ... I take everything at face value. Seems maybe you have a large amount of preconceived notions though ...

You claim to be agnostic, but you beg the question of how you believe everything got here. If you're not a Christian, creationism can't be your alternative explanation, so what is it?

Aroc,A creation theory is not solely a Christian hallmark. All religions have one. To be fair, you can say science is just attempting to provide a fuller (hopefully more accurate) explanation to the same question - it's own view of the how we got here...

I can only assume it's Christianity as it follows the trend of the rest of the Christian creationists that come here.

A fair assumption, considering the majority of creation proselytizing on an English language site would be Western . With the dominant Western religious group being Christian.

You have to admit that the infinite number of complex interactions resulting in our existence that we are now aware of can be - daunting. Making it look in the bigger picture, random (it isn't, actually. It just APPEARS that way). This might be a result of being taught math from a "sequential" perspective vs a logarithmic one (the method the Universe uses).Anyway, I can see how the creation perspective derived from the view that all these organized structures we observe seemingly form out of total randomness. Since that individual can't truly visualize a seeming infinity, his consciousness acquiesces to the "it must have been designed by someone smarter than us" paradigm.

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